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Maya Harary, David J. Segar, Kevin T. Huang, Ian J. Tafel, Pablo A. Valdes and G. Rees Cosgrove

Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.

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Timothy R. Smith, M. Maher Hulou, Kevin T. Huang, Breno Nery, Samuel Miranda de Moura, David J. Cote and Edward R. Laws


The purpose of this study was to describe complications associated with the endonasal, transsphenoidal approach for the treatment of adrenocorticotropic hormone (ACTH)–positive staining tumors (Cushing's disease [CD] and silent corticotroph adenomas [SCAs]) performed by 1 surgeon at a high-volume academic medical center.


Medical records from Brigham and Women's Hospital were retrospectively reviewed. Selected for study were 82 patients with CD who during April 2008–April 2014 had consecutively undergone transsphenoidal resection or who had subsequent pathological confirmation of ACTH-positive tumor staining. In addition to demographic, patient, tumor, and surgery characteristics, complications were evaluated. Complications of interest included syndrome of inappropriate antidiuretic hormone secretion, diabetes insipidus (DI), CSF leakage, carotid artery injury, epistaxis, meningitis, and vision changes.


Of the 82 patients, 68 (82.9%) had CD and 14 (17.1%) had SCAs; 55 patients were female and 27 were male. Most common (n = 62 patients, 82.7%) were microadenomas, followed by macroadenomas (n = 13, 14.7%). A total of 31 (37.8%) patients underwent reoperation. Median follow-up time was 12.0 months (range 3–69 months). The most common diagnosis was ACTH-secreting (n = 68, 82.9%), followed by silent tumors/adenomas (n = 14, 17.1%). ACTH hyperplasia was found in 8 patients (9.8%). Of the 74 patients who had verified tumors, 12 (16.2%) had tumors with atypical features.

The overall (CD and SCA) rate of minor complications was 35.4%; the rate of major complications was 8.5% (n = 7). All permanent morbidity was associated with DI (n = 5, 6.1%). In 16 CD patients (23.5%), transient DI developed. Transient DI was more likely to develop in CD patients who had undergone a second operation (37.9%) than in those who had undergone a first operation only (12.8%, p < 0.05). Permanent DI developed in 4 CD patients (5.9%) and 1 SCA patient (7.1%). For 1 CD patient, intraoperative carotid artery injury required endovascular sacrifice of the injured artery, but the patient remained neurologically intact. For another CD patient, aseptic meningitis developed and was treated effectively with corticosteroids. One CD patient experienced major postoperative epistaxis requiring another operative procedure to achieve hemostasis. For 2 CD patients, development of sinus mucoceles was managed conservatively. For 1 SCA patient, an abdominal wound dehisced at the fat graft site. No patients experienced postoperative CSF leakage, visual impairment, or deep vein thrombosis.


Transsphenoidal surgery is the treatment of choice for patients with CD and other ACTH-positive staining tumors. Recent advances in endoscopic technology and increasing surgeon comfort with this technology are making transsphenoidal procedures safer, faster, and more effective. Serious complications are uncommon and can be managed successfully.

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Edward R. Laws, Ian F. Parney, Wei Huang, Fred Anderson, Angel M. Morris, Anthony Asher, Kevin O. Lillehei, Mark Bernstein, Henry Brem, Andrew Sloan, Mitchel S. Berger, Susan Chang and Glioma Outcomes Investigators

Object. The Glioma Outcomes Project represents a contemporary analysis of the management of malignant (Grade III and Grade IV/GBM) gliomas in North America. This observational database was used to evaluate the influence of resection, as opposed to biopsy, on patient outcome as measured by the length of survival. Attempts were made to reduce the impact of selection bias by repeating the data analysis after omitting patients with major negative prognostic factors.

Methods. Outcome data from 788 patients accrued from multiple sites over a 4-year period (1997–2001) were analyzed with the primary outcome measure being length of survival. Of these, 565 patients with recent diagnoses formed the basis of the present analysis. Patients were systematically followed up until death or up to 24 months after enrollment in the study, and survival data were correlated with the histopathological grade and location of the tumor, the extent of surgery, the patient's performance status, and demographic factors.

The median length of survival was 40.9 weeks for patients with recently diagnosed GBMs. The true median length of survival for patients with Grade III gliomas was not reached, although there was a 58% survival rate at 104 weeks. In multivariate analysis, resection rather than biopsy (p < 0.0001), age 60 years or younger (p < 0.0001), and a Karnofsky Performance Scale (KPS) score of 70 or greater (p = 0.0004) were associated with a prolonged survival time for patients with Grade III or IV gliomas. The prognostic value of resection compared with biopsy was maintained (p < 0.0001), even after eliminating patients considered to be “poor risk” (those with age > 60 years, KPS score < 70, or presence of multifocal tumors), who may have been overrepresented in the biopsy group. Survival “tails” at 24 months were 58% for Grade III gliomas and 11% for GBMs.

Conclusions. These data provide Class II evidence to support tumor grade, patient's age, and patient's functional status as prognostic factors for survival in individuals with recently diagnosed malignant gliomas. Resection (compared with biopsy) is also a strong prognostic factor; however, no quantitative attempt was made to assess the true extent of the resection.

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Susan M. Chang, Ian F. Parney, Michael Mcdermott, Fred G. Barker II, Meic H. Schmidt, Wei Huang, Edward R. Laws Jr., Kevin O. Lillehei, Mark Bernstein, Henry Brem, Andrew E. Sloan, Mitchel Berger and the Glioma Outcomes Investigators

Object. In many new clinical trials of patients with malignant gliomas surgical intervention is incorporated as an integral part of tumor-directed interstitial therapies such as gene therapy, biodegradable wafer placement, and immunotherapy. Assessment of toxicity is a major component of evaluating these novel therapeutic interventions, but this must be done in light of known complication rates of craniotomy for tumor resection. Factors predicting neurological outcome would also be helpful for patient selection for surgically based clinical trials.

Methods. The Glioma Outcome Project is a prospectively compiled database containing information on 788 patients with malignant gliomas that captured clinical practice patterns and patient outcomes. Patients in this series who underwent their first or second craniotomy were analyzed separately for presenting symptoms, tumor and patient characteristics, and perioperative complications. Preoperative and intraoperative factors possibly related to neurological outcome were evaluated.

There were 408 patients who underwent first craniotomies (C1 group) and 91 patients who underwent second ones (C2 group). Both groups had similar patient and tumor characteristics except for their median age (55 years in the C1 group compared with 50 years in the C2 group; p = 0.006). Headache was more common at presentation in the C1 group, whereas papilledema and an altered level of consciousness were more common at presentation in patients undergoing second surgeries. Perioperative complications occurred in 24% of patients in the C1 group and 33% of patients in the C2 group (p = 0.1). Most patients were the same or better neurologically after surgery, but more patients in the C2 group (18%) displayed a worsened neurological status than those in the C1 group (8%; p = 0.007). The Karnofsky Performance Scale score and, in patients in the C2 group, tumor size were important neurological outcome predictors. Regional complications occurred at similar rates in both groups. Systemic infections occurred more frequently in the C2 group (4.4 compared with 0%; p < 0.0001) as did depression (20 compared with 11%; p = 0.02). The perioperative mortality rate was 1.5% for the C1 group and 2.2% for the C2 group (p = not significant). The median length of the hospital stay was 4 days in each group.

Conclusions. Perioperative complications occur slightly more often following a second craniotomy for malignant glioma than after the first craniotomy. This should be considered when evaluating toxicities from intraoperative local therapies requiring craniotomy. Nevertheless, most patients are neurologically stable or improved after either their first or second craniotomy. This data set may serve as a benchmark for neurosurgeons and others in a discussion of operative risks in patients with malignant gliomas.